Bactericidal and bacteriostatic preparations comprising 2, 3-diaryl indoles



Patented June 6, 1950 UNITED STATES PATENT OFFICE BACTERICIDAL ANDBACTERIOSTATIC PREPARATIONS COMPRISING 2,3-DI- ARYL INDOLES John H.Standen, Yonkers, N. Y., assignorto The B. F. GoodrichCompany, New York,N. Y., a corporation of New York No Drawing. Application May 18, 1948,Serial No. ?7,824=

2 Claims.

wherein Ar is an aryl hydrocarbon radical or the benzene series such asphenyl, tolyl, xylyl, cumyl,

etc. They may be made by the condensation of aniline with a compound ofthe structure according to the equation: H NH: Ar--C-(liAr a Forexample, 2,3-diphenyl indole, the compound preferably used in thisinvention, can be prepared by the condensation of benzoin and aniline inthe presence of zinc chloride as described in German Patent 574,840.

It is quite surprising that these 2,3-diary1 indoles possess markedbactericidal activity inasmuch as it has been reported in the literaturethat bacteria belonging to Escherichia, Aerobacter, and Staphylococcusgenera are most resistant to the parent unsubstituted indole,

The following specific examples illustrate the 2 bactericidal andbacteriostatic activity 2,3- diaryl indoles.

EXAMPLE I Varying amounts of 2,3-diphenyl indole were added to ml.portions of nutrient broth (Difco) and each portion inoculated withStaphylococcus aureus. The test samples were incubated for 24 hours at40 C. (fever heat). After the incubation period, the treated brothsamples were examined to determine bacterial growth. The results of thistest are tabulated below in Table I.

Table I' 2,3-DIPHEN'YL IN'DOLE IN NUTRIENT BROTH Concentration Growth ofStaphylococcus aureus 24 P. P. M. hours at 40 C.

2,3-diphenyl indole was also employed against Staphylococcus aureus,Escherichia coli, and Mycobacterium tuberculi in agar plate tests, Inthese tests, 2,3-diphenyl indole was dissolved in alcohol and thealcohol solution was dispersed in sufficient water to give the desiredconcentration. This aqueous dispersion was employed to prepare the agar(Difco nutrient agar) which was poured into sterile Petri dishes, theagar and dishes were sterilized by autoclaving, and the agar wasinoculated with the bacteria. The dishes containing inoculated agar wereincubated for 3 days at temperatures from 21 C. to 40 C. Untreated,autoclaved agar inoculated with these bacteria were also incubated as acheck on the growth activity of the bacteria. The results obtained areshown in the following Tables 11, D1 and IV:

Table II Incubation Dairyi indole Concentration,

P. P. M. Temp. O.

Bacteria Growth None. D

Table I?! 2, 3-DIPHENYL INDOLE 1N AGA R [Growth of Escherichia coZi-3day incubation] Table IV 2, 3-DIPHENYL INDOLE IN AGAR [Growth ofMycobacierium tuberculi3 day incubation] Diary] IndlolePClolncentration.llnglixlllgatgrn Bacteria Growth 21 None.

21 Trace.

21 Good.

37 None.

37 Excellent.

40 None.

40 Good.

The data in the tables above clearly demonstrate the remarkableeffectiveness of 2,3-diphenyl indole as a bactericide at concentrationsas low as one P.P.M. and at temperatures ranging from 21 to 40 C. Other2,3-diaryl indoles such as the 2,3-ditlyl indoles can be employed in thesame manner and in the same concentrations as described above withsubstantially the same results. It will be understood that higherconcentrations of the active agent are also effective and may beemployed, if desired, although use of as little active agent as iseffective is ordinarily to be preferred for economic reasons.

This invention also contemplates the control of bacteria with 2,3-diarylindoles in various other ways including the application of the diarylindole to bacteria wherever present and the incorporation of the diarylindole in substances and materials which normally support and nourishsuch growth. For example, these compounds may be employed asbactericides in cosmetics such as hand creams, face creams, shavingcreams, soaps, and the like where oily materials that will nourishbacteria are normally present. In addition, they may be used asbactericides in compositions containing proteinous materials. The2,3-diaryl indoles may also be used to disinfect cutlery, china ware andany utensil used in the preparation of food. They may also be used todisinfect tools, instruments, iioors, walls,

beds, furniture and the like.

The 2,3-diaryl indoles can be applied to bacteria as aqueous solutionswhere the solubility will permit the formation of such solutions havinga. toxic concentration or they may be employed as aqueous dispersionseither with or without a wetting agent. Similarly, the diaryl indole canbe applied as a solution in a suitable solvent such as acetone oralcohol. The diaryl indoles may also be dispersed in oils, fats andgreases to be applied in a protective film or 10- tion or may beincorporated in such finely-divided solids as for example talc, clays,zinc ox ide, corn starch, and the like. In short, the 2 ,3-diaryl indolemay be dispersed, dissolved or otherwise uniformly associated with amajor proportion of a carrier medium to obtain bactericidal andbacteriostatic preparations and compositions of wide utility incontrolling bacterial growth. Such preparations and compositions willcontain a concentration of the diaryl indole sufficient to preventbacterial growth but the concentration will in general be less than 5%by weight of the entire preparation.

Having disclosed specific examples of my invention, I do not desire orintend to limit myself solely thereto for, as hitherto stated, theconcentrations of active ingredients may be varied REFERENCES CITED Thefollowing references are of record in the file of this patent:

FOREIGN PATENTS Country Date Germany Apr. 20, 1933 OTHER REFERENCESChem. Abstracts, vol. 41, page 3576a (1947).

Number

2. A BACTERIAL AND BACTERIOSTATIC PREPARATION COMPRISING FROM 1.0 PARTPER MILLION TO 5% BY WEIGHT OF 2,3-DIPHENYL INDOLE DISPERSED IN WATER.